A catalog of genetic loci associated with kidney function from analyses of a million individuals: Nature Genetics

M Wuttke, Y Li, M Li, KB Sieber, MF Feitosa, M Gorski, A Tin, L Wang, AY Chu, A Hoppmann, H Kirsten, A Giri, JF Chai, G Sveinbjornsson, BO Tayo, T Nutile, C Fuchsberger, J Marten, M Cocca, S GhasemiY Xu, K Horn, D Noce, PJ van der Most, S Sedaghat, Z Yu, M Akiyama, S Afaq, TS Ahluwalia, P Almgren, N Amin, J Ärnlöv, SJL Bakker, N Bansal, D Baptista, S Bergmann, ML Biggs, G Biino, M Boehnke, E Boerwinkle, M Boissel, EP Bottinger, TS Boutin, H Brenner, M Brumat, R Burkhardt, AS Butterworth, E Campana, A Campbell, H Campbell, M Canouil, RJ Carroll, E Catamo, JC Chambers, ML Chee, X Chen, CY Cheng, Y Cheng, K Christensen, R Cifkova, M Ciullo, MP Concas, JP Cook, J Coresh, T Corre, CF Sala, D Cusi, J Danesh, EW Daw, MH de Borst, A De Grandi, R de Mutsert, APJ de Vries, F Degenhardt, G Delgado, A Demirkan, E Di Angelantonio, K Dittrich, J Divers, R Dorajoo, KU Eckardt, G Ehret, P Elliott, K Endlich, MK Evans, JF Felix, VHX Foo, OH Franco, A Franke, BI Freedman, S Freitag-Wolf, Y Friedlander, P Froguel, RT Gansevoort, H Gao, P Gasparini, JM Gaziano, V Giedraitis, C Gieger, G Girotto, F Giulianini, M Gögele, SD Gordon, DF Gudbjartsson, V Gudnason, T Haller, P Hamet, TB Harris, CA Hartman, C Hayward, JN Hellwege, CK Heng, AA Hicks, E Hofer, W Huang, N Hutri-Kähönen, SJ Hwang, MA Ikram, OS Indridason, E Ingelsson, M Ising, VWV Jaddoe, J Jakobsdottir, JB Jonas, PK Joshi, NS Josyula, B Jung, M Kähönen, Y Kamatani, CM Kammerer, M Kanai, M Kastarinen, SM Kerr, CC Khor, W Kiess, ME Kleber, W Koenig, JS Kooner, A Körner, P Kovacs, AT Kraja, A Krajcoviechova, H Kramer, BK Krämer, F Kronenberg, M Kubo, B Kühnel, M Kuokkanen, J Kuusisto, M La Bianca, M Laakso, LA Lange, CD Langefeld, JJ Lee, B Lehne, T Lehtimäki, W Lieb, Lifelines Cohort Study, SC Lim, L Lind, CM Lindgren, J Liu, M Loeffler, RJF Loos, S Lucae, MA Lukas, LP Lyytikäinen, R Mägi, PKE Magnusson, A Mahajan, NG Martin, J Martins, W März, D Mascalzoni, K Matsuda, C Meisinger, T Meitinger, O Melander, A Metspalu, EK Mikaelsdottir, Y Milaneschi, K Miliku, PP Mishra, V. A. Million Veteran Program, KL Mohlke, N Mononen, GW Montgomery, DO Mook-Kanamori, JC Mychaleckyj, GN Nadkarni, MA Nalls, M Nauck, K Nikus, B Ning, IM Nolte, R Noordam, J O'Connell, ML O'Donoghue, I Olafsson, AJ Oldehinkel, M Orho-Melander, WH Ouwehand, S Padmanabhan, ND Palmer, R Palsson, BWJH Penninx, T Perls, M Perola, M Pirastu, N Pirastu, G Pistis, AI Podgornaia, O Polasek, B Ponte, DJ Porteous, T Poulain, PP Pramstaller, MH Preuss, BP Prins, MA Province, TJ Rabelink, LM Raffield, OT Raitakari, DF Reilly, R Rettig, M Rheinberger, KM Rice, PM Ridker, F Rivadeneira, F Rizzi, DJ Roberts, A Robino, P Rossing, I Rudan, R Rueedi, D Ruggiero, KA Ryan, Y Saba, C Sabanayagam, V Salomaa, E Salvi, KU Saum, H Schmidt, R Schmidt, B Schöttker, CA Schulz, N Schupf, CM Shaffer, Y Shi, AV Smith, BH Smith, N Soranzo, CN Spracklen, K Strauch, HM Stringham, M Stumvoll, PO Svensson, S Szymczak, ES Tai, SM Tajuddin, NYQ Tan, KD Taylor, A Teren, YC Tham, J Thiery, CHL Thio, H Thomsen, G Thorleifsson, D Toniolo, A Tönjes, J Tremblay, I Tzoulaki, AG Uitterlinden, S Vaccargiu, RM van Dam, P van der Harst, CM van Duijn, DR Velez Edward, N Verweij, S Vogelezang, U Völker, P Vollenweider, G Waeber, M Waldenberger, L Wallentin, YX Wang, C Wang, DM Waterworth, W Bin Wei, H White, JB Whitfield, SH Wild, JF Wilson, MK Wojczynski, C Wong, TY Wong, L Xu, Q Yang, M Yasuda, LM Yerges-Armstrong, W Zhang, AB Zonderman, JI Rotter, M Bochud, BM Psaty, V Vitart, JG Wilson, A Dehghan, A Parsa, DI Chasman, K Ho, AP Morris, O Devuyst, S Akilesh, SA Pendergrass, X Sim, CA Böger, Y Okada, TL Edwards, H Snieder, K Stefansson, AM Hung, IM Heid, M Scholz, A Teumer, A Köttgen, C Pattaro

Research output: Contribution to journalArticle

Abstract

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
Original languageEnglish
Pages (from-to)957-972
Number of pages16
JournalNature Genetics
Volume51
Issue number6
DOIs
Publication statusPublished - 2019

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    Wuttke, M., Li, Y., Li, M., Sieber, KB., Feitosa, MF., Gorski, M., Tin, A., Wang, L., Chu, AY., Hoppmann, A., Kirsten, H., Giri, A., Chai, JF., Sveinbjornsson, G., Tayo, BO., Nutile, T., Fuchsberger, C., Marten, J., Cocca, M., ... Pattaro, C. (2019). A catalog of genetic loci associated with kidney function from analyses of a million individuals: Nature Genetics. Nature Genetics, 51(6), 957-972. https://doi.org/10.1038/s41588-019-0407-x